title: Metallopanstimulin-1 regulates invasion and migration of gastric cancer cells partially through integrin β4.
abstract: MPS-1 (metallopanstimulin-1), also known as ribosomal protein S27, was overexpressed in gastric cancer cells. However, how MPS-1 contributes to gastric carcinogenesis has not been well characterized. Here, we show that high expression of MPS-1 was observed in gastric cancer tissues and associated with gastric cancer cell metastasis. Alteration of MPS-1 expression regulates invasion and migration of gastric cancer cells both in vitro and in vivo. Furthermore, by using Signal-Net and cluster analyses of microarray data we identified integrin β4 (ITGB4) as a downstream target of MPS-1 that mediates its effects on cell metastasis. Knockdown of MPS-1 expression in gastric cancer cells led to significant reduction of ITGB4 expression at both the RNA and protein levels. Mechanically, we found that overexpression of ITGB4 in MPS-1 knockdown cells largely recovers the ability of invasion and migration. Conversely, knockdown of ITGB4 partially reduced cell invading/migrating ability induced by MPS-1 overexpression. Moreover, MPS-1 and ITGB4 expressions are positively correlated in gastric cancer cell lines and tissues. Finally, the survival analyses show that the expression of MPS-1 and ITGB4 is associated with poor outcomes in gastric cancer patients. Collectively, our findings suggest that MPS-1 regulates cell invasiveness and migration partially through ITGB4 and that MPS-1/ITGB4 signaling axis may serve as therapeutic targets in the treatment of gastric cancer.
authors.affiliation: Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Yang
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Bing-Ya
authors.initials: BY
authors.lastname: Liu
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Wu
authors.forename: Qin-Long
authors.initials: QL
authors.lastname: Gu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C059834:ITGB4 protein, human; D039663:Integrin beta4; D008667:Metalloproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; D012269:Ribosomal Proteins